ORCID Profile
0000-0003-1619-9598
Current Organisation
University of South Australia
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Publisher: Elsevier BV
Date: 06-2022
DOI: 10.1016/J.NANO.2022.102546
Abstract: Sentinel lymph node biopsy in cancers of the head and neck offers demonstrated clinical and diagnostic value, but adoption is limited by concerns about the detrimental consequence to survival of false negative results in a highly curable setting. The aim of this study was to demonstrate potential to overcome this via application of a novel mannose-labeled magnetic iron oxide tracer. In a large animal model, preoperative imaging and intraoperative magnetometer detection were used to identify magnetic lymph nodes. Iron quantification mapped the distribution of tracer within lymphatic levels. Over a 4-week test period, uptake of magnetic tracer in lymph nodes increased in a linear-like fashion, with a substantial percentage of accumulated iron (83%) being retained in the sentinel node. This result indicates a high affinity of mannose-labeled particles to the sentinel node, while providing a means for the magnetometer probe to indicate node status based on intraoperative signal.
Publisher: Wiley
Date: 08-09-2022
DOI: 10.1002/HED.27177
Abstract: Sentinel lymph node biopsy (SLNB) is a staging procedure dependent on accurate mapping of draining lymphatics via tracers. Robot‐assisted SLNB enables access to multiple neck levels with a single incision and intraoperative fluorescence guidance to the SLN. Lymphatic mapping in swine was done using a magnetic tracer and fluorescent dye, injected into the tongue. MRI preoperatively mapped lymphatic spread of the magnetic tracer. Dissection was performed using a da Vinci Xi robot guided by fluorescence‐imaging of the dye. Robot‐assisted SLNB was successfully performed in all animals ( n = 5). A novel MRI protocol differentiated SLNs ( n = 6) from lower echelon nodes ( n = 11) based on flow progression. Fluorescence imaging provided valuable intraoperative guidance and correlated with magnetic‐positive nodes. This study demonstrates preclinical feasibility of a robot‐assisted approach to SLNB using magnetic and fluorescent tracers in the head and neck, enabling both preoperative mapping and intraoperative guidance.
Publisher: Cold Spring Harbor Laboratory
Date: 12-06-2022
DOI: 10.1101/2022.06.10.495719
Abstract: Accurate and precise delineation of gross tumour volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumours, such as prostate cancer. Magnetic resonance imaging of tumour molecular targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI-LINAC. Fibroblast activation protein (FAP) is a transmembrane protein overexpressed in stromal components of % of epithelial carcinomas. Herein we compare targeted MRI of gold standard PSMA with FAP in the delineation of orthotopic tumours in a mouse model of prostate cancer. Control (no ligand), FAP and PSMA-targeting iron oxide nanoparticles were prepared with modification of an MRI agent (FerroTrace). Mice with orthotopic LNCaP tumours underwent T 2 -weighted 3D MRI 24 hours after intravenous injection of contrast agents. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles, which was most pronounced on the tumour periphery. FAP-targeted MRI increased the proportion of tumour contrast enhancing black pixels by 13.37% when compared to PSMA. Furthermore, analysis of changes in R2 values between healthy prostates and LNCaP tumours indicated an increase in contrast enhancing pixels in the tumour border of 15%, when targeting FAP, in contrast to PSMA This study demonstrates preclinical feasibility of PSMA and FAP-targeted MRI which can enable targeted image-guided focal therapy of localized prostate cancer.
Publisher: Royal Society of Chemistry (RSC)
Date: 2023
DOI: 10.1039/D2NR05619D
Abstract: Magnetic extracellular vesicle (EV) enrichment using antibody conjugated bacteria-derived iron oxide nanowires coupled with mass spectrometry-based proteome profiling enables efficient EV subtype enrichment and reproducible proteomics.
Publisher: Wiley
Date: 25-02-2023
Abstract: Accurate delineation of gross tumor volumes remains a barrier to radiotherapy dose escalation and boost dosing in the treatment of solid tumors, such as prostate cancer. Magnetic resonance imaging (MRI) of tumor targets has the power to enable focal dose boosting, particularly when combined with technological advances such as MRI‐linear accelerator. Fibroblast activation protein (FAP) is overexpressed in stromal components of % of epithelial carcinomas. Herein, the authors compare targeted MRI of prostate specific membrane antigen (PSMA) with FAP in the delineation of orthotopic prostate tumors. Control, FAP, and PSMA‐targeting iron oxide nanoparticles were prepared with modification of a lymphotropic MRI agent (FerroTrace, Ferronova). Mice with orthotopic LNCaP tumors underwent MRI 24 h after intravenous injection of nanoparticles. FAP and PSMA nanoparticles produced contrast enhancement on MRI when compared to control nanoparticles. FAP‐targeted MRI increased the proportion of tumor contrast‐enhancing black pixels by 13%, compared to PSMA. Analysis of changes in R2 values between healthy prostates and LNCaP tumors indicated an increase in contrast‐enhancing pixels in the tumor border of 15% when targeting FAP, compared to PSMA. This study demonstrates the preclinical feasibility of PSMA and FAP‐targeted MRI which can enable targeted image‐guided focal therapy of localized prostate cancer.
Publisher: Springer Science and Business Media LLC
Date: 10-05-2023
DOI: 10.1007/S00464-023-10099-6
Abstract: Gastrectomy with extended (D2) lymphadenectomy is considered standard of care for gastric cancer to provide the best possible outcomes and pathologic staging. However, D2 gastrectomy is a technically demanding operation and reported to be associated with increased complications and mortality. Application of sentinel lymph node (SLN) concept in gastric cancer has the potential to reduce patient morbidity however, SLN techniques are not established for gastrectomy, in part due to lack of practical tracers. An effective and convenient tracer with enhanced SLN accumulation is critically needed. Mannose-labelled magnetic tracer ‘FerroTrace’ and fluorescent dye indocyanine green (ICG) were injected laparoscopically into the stomach submucosa of 8 healthy swine under general anaesthesia. Intraoperative fluorescence imaging was used to highlight draining lymphatic pathways containing ICG, while preoperative T2-weighted MRI and ex vivo magnetometer probe measurements were used to identify nodes containing FerroTrace. Lymphadenectomy was performed either robotically ( n = 2) or via laparotomy ( n = 6). Mixing ICG and FerroTrace ensured concurrence of fluorescent and magnetic signals in SLNs. An initial trial with robotic dissection removed all magnetic LNs ( n = 4). In the subsequent laparotomy study that targeted all ICG-LNs based on intraoperative fluorescence imaging, dissection removed an average of 4.7 ± 1.2 fluorescent, and 2.0 ± 1.3 magnetic LNs per animal. Both MRI and magnetometer detected 100% of SLNs ( n = 7). FerroTrace demonstrated high specificity to SLNs, which contained 76 ± 30% of total lymphotropic iron, and 88 ± 20 % of the overall magnetometer signal. Through utilisation of this dual tracer approach, SLNs were identified via preoperative MRI, visualised intraoperatively with fluorescence imaging, and confirmed with a magnetometer. This combination pairs the sensitivity of ICG with SLN-specific FerroTrace and can be used for reliable SLN detection in gastric cancer, with potential applications in neoadjuvant therapy.
Publisher: Cold Spring Harbor Laboratory
Date: 05-2022
DOI: 10.1101/2022.05.01.490183
Abstract: Immuno-specific enrichment of extracellular vesicles (EVs) originating from specific cells/tissues is a promising source of information towards improving insights into cellular pathways underpinning various pathologies and developing novel non-invasive diagnostic methods. Enrichment is an important aspect in mass spectrometry-based analyses of EVs. Herein, we report a protocol for immuno-magnetic enrichment of subtype specific EVs and their subsequent processing for mass spectrometry. Specifically, we conjugated placental alkaline phosphatase (PLAP) antibodies to magnetic iron oxide nanowires (NWs) derived from bacterial biofilms and demonstrated the utility of this approach by enriching placental specific EVs (containing PLAP) from cell culture media. We demonstrate efficient PLAP+ve EV enrichment for both NW-PLAP and Dynabeads™-PLAP, with PLAP protein recovery (83.7±8.9% and 83.2±5.9%, respectively), high particle-to-protein ratio (7.5±0.7×10 9 and 7.1 ± 1.2×10 9, respectively), and low non-specific binding of non-target EVs (7±3.2% and 5.4±2.2%, respectively). Furthermore, our optimized EV enrichment and processing approach identified 2518 and 2545 protein groups with mass spectrometry for NW-PLAP and Dynabead™-PLAP, respectively, with excellent reproducibility (Pearson correlation 0.986 and 0.988). The proposed immuno-specific EVs enrichment and liquid chromatography-tandem mass spectrometry method using naturally occurring iron oxide magnetic NWs or gold-standard Dynabeads™ enables high-quality EV proteomic studies.
No related grants have been discovered for Valentina Milanova.